Association of intensive chemotherapy with the rate of pathogenic driver mutation clearance in acute myeloid leukemia.
Authors: Ruby Maini, Susan Olet, Emma Hillis, Raina Saxena, Carl Haupt, Ernest Philon, Carter Thomas Davis
Journal: Journal of Clinical Oncology (2023)

7040 Background: Identification of pathogenic molecular mutations (PMM) as drivers in the development of acute myeloid leukemia (AML) and in initial prognostic assessment has become clinical practice. Persistence of PMM in a morphologic leukemia free state is correlated with high risk of relapse and poor prognosis. Therapy for induction of remission and elimination of all markers of residual disease remains controversial, especially with the addition of venetoclax to hypomethylating agents (HMA). Here we compare the rates of PMM clearance between intensive chemotherapy (IC) and less intensive chemotherapy (LIC) regimens. Secondary, we assessed differences in ethnicity between white and black patients (pts). Methods: Retrospective study from a leukemia treatment center in Louisiana. De-identified pt records from 2018-2022 assessed for demographics: race, age, sex and diagnosis: AML, ELN 2017 staging, and mortality by IC vs. LIC regimen. IC included anthracycline and cytarabine containing regimens. LIC included HMA, with or without venetoclax. Chi-Squared analysis preformed, threshold for significance at p &lt; 0.05. Results: 408 pts with non-M3 AML who underwent treatment, 180(44.1%) were female, 91(22.3%) were black, 303(74.3%) were white, 273(66.9%) received IC while 135(33.1%) received LIC. NGS found a total of 280 pre-treatment PMM. Among 217 pts who received treatment, the rate of mutation clearance with IC was 55.2%, compared with 50.8% LIC(p = 0.55). Stratifying by race, black pts had a twofold mutation clearance compared to white pts OR = 1.76, 95% CL (0.91 – 3.44). Similar proportions of pts received LIC vs IC among both white (74.1% vs 74.4%) and black (22.2% vs 22.3). There was no statistically significant difference for overall survival on chemotherapy regimen intensity (p = 0.1991), race (p = 0.2736), or gender (p = 0.6912). Conclusions: In our study, PMM clearance was similar between IC and LIC inductions. Although these findings are from a single center, the ability to clear driver mutations at a similar rate to IC may offer a significant advantage of LIC with venetoclax. Mutation clearance is often used as a surrogate marker for residual disease, it may be reasonably inferred that these regimens serve as suitable induction regimens for pts who may be considered for allogeneic stem cell transplantation. Blacks make up a greater proportion of the population in Louisiana (~33%) as compared to the national average (~13%). Often underrepresented in prospective clinical trials, blacks made up 22.7% of subjects providing increased insight to clinical responses. No difference in mortality based on race and a trend toward greater mutational clearance in blacks. Emphasizing the importance of standardizing care in treatment centers and the need for greater representation in prospective clinical trials to understand better how differences in race may impact treatment outcomes.